LV15082B - Cream for restoring epidermal lipid barrier of the facial skin, neck and decollette area in metabolic syndrome patients - Google Patents

Abstract

The invention relates to the field of medicine, namely family medicine (general practitioners), therapy, endocrinology, gerontology, dermatology and cosmetology and solves the problem of restoration of epidermal lipid barrier in facial skin, decollete and the neck in metabolic syndrome patients. The goal of the invention is to develop a cream composition that restores epidermal lipid barrier and lipid layer of facial skin, neck and decollete for use in patients with metabolic syndrome. Set goals are achieved through the design of a specific ē cream composition, which contains seleno-L-methionine, Vitamin E alpha-tocopherol, squalane, methyl-4- hydroxybenzoate, glycerol monostearate 60, cetylalchol, middle chain triglyceride, white petrolatum, macrogol-20-glycerolmonostearate, 1,2-propanediol and distilled water in the certain ratios mass relationships.

Description

DESCRIPTION OF THE INVENTION

The invention relates to medicine, relates to family medicine (family doctors' practice), therapy, endocrinology, gerontology, dermatology and cosmetology, and solves the problems of restoring the epidermal lipid barrier of the facial skin, neck and décolleté in patients with metabolic syndrome.

TECHNICAL LEVEL

Metabolic syndrome (MS), a complex of changes associated with metabolic disturbances in which insulin sensitivity is impaired and cellular glucose uptake is impaired. Metabolic syndrome is followed by a complex of diseases: hypertension, obesity, ischemic heart disease, type 2 diabetes. The development of the metabolic syndrome is characterized by an increase in waist circumference: more than 102 cm for men and 88 cm for women. Arterial blood pressure level 135/85 mmHg. High levels of lipid peroxidation products are stored in the blood. Oxidants begin to activate cellular reactions that destroy proteins, lipids, DNA. The barrier function of the skin is impaired and intensively loses moisture, becomes dry, causing excessive flaking, thickening of the horny layer of the skin, giving the skin a gray tint, and promoting the development of various skin conditions: seborrhea, atrophic dermatitis, psoriasis, eczema, etc. diseases [1].

Human body skin is a complex biological tissue system made up of epidermis, denna and subcutaneous fat cells. The basal layer of the epidermis contains melanocytes and Langerhans cells located on the basement membrane. The basal layer of the epidermis contains a protoplasmic, granular layer. forms cells with keratohialin complexes. Denna - the connecting part of the skin, the main volume of the skin. Dermis with basal membrane isolated from epidermis [2],

The outer part of the epidermis is covered by a stratum corneum, on which a water-lipid mantle with a slightly acidic environment is created, with an acidity of 4.5 to 5.5 pH. This level of acidity produces bactericidal effects and promotes lipid synthesis. The acid properties of the skin are associated with perspiration and skin fat. Many microbes that penetrate the skin die within 20-30 minutes [3], and the water-lipid mantle forms an epidermal barrier made up of horny cells called scales called "comaocytes", between which epidermal intercellular lipids, ceramides, are located. Ceramides bind comaocytes in an impermeable, integral epidermal barrier. Ceramide molecules have a polar structure because they have hydrophilic heads (preferable to water) and lipophilic tails (preferable to fat). The epidermal lipid barrier prevents the entry of harmful substances into the skin, and regulates the hemostasis of the dermis water. The lipid barrier consists of cholesterol, ceramides, unsaturated fatty acids (Omega-3, Omega-6). Unsaturated fatty acids Omega-3, Omega-6 have anti-inflammatory properties, stimulate Langerhans cells and strengthen the epidermal lipid barrier [4]. The free fatty acids are located in the lipid layer, around the ceramides, they promote the water-impermeable function of the skin and form a water-in-oil emulsion. If the lipid barrier is disturbed, microorganisms, chemical and other exogenous aggressive factors enter the skin.

The skin has an immune cell system, with Langerhans cells (2-5% of cells in the epidermis) playing a key role. Langerhans cells are involved in killing bacteria and initiate an immune response involving dermal dendritic cells, epidermal macrophages, and so on. Skin aging is linked to the condition of the immune system [5]. After the age of 25, the body starts a natural aging mechanism: the amount of skin macrophages decreases, oxidants begin to activate cellular responses, causing protein, lipid and DNA damage. the process of accelerated, abnormal skin aging is particularly active in patients with metabolic syndrome (MS). · It is known · that the metabolic syndrome is accompanied by latent inflammation leading to the activation of peroxidation processes. The accumulation of lipid peroxidation products, and lipid oxidative damage of lipoproteins and lipid layer, is manifested as morphological changes in the components of the skin structure [6]. The defense system formed by antioxidants is weakened and / or ineffective in patients with metabolic syndrome. Metabolic syndrome causes oxidative stress: disruption of keratinocyte formation, increased loss of transepidermal water, dry skin, cracks and erosion. Changes · cause an imbalance of the microflora of the skin and an increase in the number of fungi, papillomas. Restoration of the skin epidermal lipid barrier in patients with metabolic syndrome is a particularly urgent task [7].

Table 1 - Analysis of skin · epidermal lipid barrier disorders and methods for their detection. .

Table 1

Analysis of skin epidermal lipid barrier disorders and methods for their detection Clinical manifestations of disorders Acceleration of transepidental water loss (paternity) and water content in the stratum corneum (corneaometry). Dry skin, flaking, cracking, thickening of the stratum corneum (hyperkeratosis). Changes in skin acid-base balance, pH (pH-metric sensor). Papillomas, skin infections, lipid synthesis disorders. Skin relief and morphological condition (dermatoscopy, photomicrography). Skin turgor, micro relief, papillomas, loss of elasticity, elastosis. Pigmentation and flaking (siascopy, mexametry). Lentigo organs and / or heterogeneity of pigmentation (dispigmentation). Skin immunity (light microscopy, immunohistochemistry). Penetration of immunocompetent Langerhans cells, Birbek granules, bacteria and / or viruses, papillomas. Oily areas of the skin (sebummetry). Dry, oily, normal, combination skin. Epidermal proliferation rate (Microphotography). Comeocyte Size, Large Comeocyte Cells in Skin Dehydration.

Analysis of skin epidermal lipid barrier disorders is performed through dermatoscopy (assessment of skin pH, moisture / dryness, oilyness) and siascopy (assessment of dispigmentation and microrelief study). Tewameter® TM 300, Courage + Khazaka electronic GmbH, Germany, is used to measure transepidermal water loss. MiasViesv SIAscope V · 'Handset, Astron, United Kingdom is used to carry out the siascope. HEINE alpha + Heine Optotechnic, Germany, is used for dermatoscopy. By using them, the parameters transmitted to the computer are analyzed, while several characteristics reflecting the state of the epidermal lipid barrier are analyzed [8-11]:

• Corneometry (moisture of the skin, water content in the stratum corneum of the epidermis), used with the help of a dermatoscope. The principle of comometry is based on the measurement of the electrical capacity of the dielectric medium. Any change in the dielectric constant associated with fluctuations in the water content of the skin's upper layers causes a change in the capacitance characteristics of the measuring system. Wetting is evaluated on a scale. The basis is the dielectric capacity of the water - 81, distinguishes 4-6 degrees of skin moisture (very high degree of humidity - 45.0-99.9; high, normal 4

35.1 -40.0; depressed, low -20.1 to 29.9; dehydrated - below 20.0).

• Measurement of transepidermal water loss, a measurement of water evaporation from the skin surface based on the principle of diffusion in an open chamber. The method is based on measuring the partial pressure of water in a closed chamber with a single humidity sensor. The increase in partial pressure in the chamber over a period of time is measured.

• Acid-base balance, pH-metry. The pH meter uses a very precise glass electrode.

• Sebummetry, a sebummetric technique used to determine the oily nature of different areas. The method is based on the principle of photometry. A polymer film is used, which is a selective lipid absorber, which is placed on the skin surface of the photometer before and after application of the transmitter. Measurement results are expressed in mcg / cm. Sebummetry scores are independent of skin moisture. The grease sensor (bronze) consists of three components, one of which is paper - matte, sensitive to fat components, which reacts only to sebum (skin fat), absorbs it, the microprocessor processes the resulting discoloration to determine skin type: dry, normal, oily or combined.

• Mexometry (an estimate of the content of various skin pigments), allows you to measure the amount of melatonin pigment in the skin and the degree of erythema. The principle of measurement is based on the fact that the skin absorbs light waves of different lengths in different areas of the spectrum. The Mexometric method is particularly useful for the numerical evaluation of an allergy or inflammatory response to ultraviolet damage.

• Micro relief research with micro photography - use of modern digital equipment for evaluation of skin surface relief and microstructure (wrinkle, smoothness, roughness) with subsequent preservation of images and possibility to compare and analyze measurements during treatment course. The exfoliation of the skin depends mainly on the rate of epidermal proliferation as well as on the water balance. Normally, the outgoing comocytes are about the same, small size. The large numbers of large cells indicate skin damage and dehydration.

Known cosmetic compositions for the prevention and treatment of dry skin in the case of ultraviolet (UV) damage. Known compositions contain plant extracts and components in combination with various oils [12-14]. It is known that the pro-oxidative effect of UV can be corrected by vitamin-antioxidants [15-21]. Known use of retinoids to prevent UV damage [22]. A topical cream with selenomethionine for topical application during insolation to protect against skin cancer is known [23]. Known use of high-ceramic moisturizing creams for use in children with atopic dermatitis [24],

Known use of moisturizers for dry skin treatment [25-26]. The use of creams containing tocopherol as an antioxidant for protection against UV damage of the skin is known [27].

Known moisturizers and emollients, which alleviate the symptoms of dry skin, improve skin hydration but do not restore it, nor do they solve the problem of restoring the epidermal lipid barrier in patients with metabolic syndrome.

Known petroleum jelly [28] which is used to temporarily replace a damaged skin barrier. Petroleum jelly and preparations based thereon are used after medical and cosmetic procedures involving removal of the stratum corneum, such as laser skin polishing, dermabrasion (mechanical removal of the epidermis), peeling. Vaseline deficiency is poor absorption in the skin, because the skin is covered with a greasy layer, which complicates its use. Vaseline has a strong occlusal effect (blocking moisture vapor), leading to skin permeability disorders and side effects. Vaseline is recommended for use only in cases of acute damage to the epidermal barrier, where it is necessary to prevent a particularly active skin cell reaction that has suddenly lost its external protection, and in situations where the skin itself is unable to form a complete barrier. In other cases blocking the evaporation of water through the damaged stratum corneum is not recommended.

A known fat emulsion that can simultaneously moisturize and nourish the skin [29]. The known fat emulsion does not have a protective effect against skin aging processes caused by damage to free radicals of the skin in patients with metabolic syndrome.

Known cream with selenium and vitamin E [30], a highly dispersed refined mink oil emulsion in water stabilized with wax emulsion. The cream does not prevent the restoration of the lipid barrier in patients with metabolic syndrome. In addition, prolonged use of a high water content cream slows down the regeneration of the stratum corneum, which adversely affects the skin of patients with metabolic syndrome [31]. Various compositions of plant extracts for improving the barrier function of the skin are known [32-36]. Known compositions do not restore the lipid layer in patients with metabolic syndrome.

There is no known means to restore the epidermal lipid barrier in patients with metabolic syndrome.

SUMMARY OF THE INVENTION

AIM AND TECHNICAL PROCESS OF THE INVENTION: To develop a cream composition for restoring the epidermal lipid barrier of the facial skin, neck and décolleté in patients with metabolic syndrome to prevent free radical damage to the lipid layer caused by latent inflammation inherent in metabolic syndrome:

• search for new formulation components and their relationship, • development of cream manufacturing technology, • development of optimal cream form.

The object of the present invention is that the cream comprises selenium L-methionine, α-tocopherol acetate, squalane, methyl 4-hydroxybenzoate, glycerol monostearate 60, cetyl alcohol, medium chain triglycerides, white petroleum jelly, macrogol-20-glycerol monostearate, 1, 2-propanediol and purified water. Additionally, the cream contains selenium-Lmethionine, α-tocopherol acetate, squalane, methyl 4-hydroxybenzoate, glycerol monostearate 60, cetyl alcohol, medium chain triglycerides, white petroleum jelly, macrogol20-glycerol monostearate, 1,2-propanediol and purified water. mass ratio g (%):

selenium-L-methionine 0.0005-0.0015; α-tocopherol acetate 0.50-1.50; squalane 11.25-18.75; methyl 4-hydroxybenzoate 0.05-0.15; glycerol monostearate 60 2.52-4.20; cetyl alcohol 3.78-6.29; medium chain triglycerides 4.72-7.87; white petroleum jelly 16.05-26.74; macrogol-20-glycerol monostearate 4.40-7.34; 1,2-Propanediol 6.29-10.49; purified water to 100.0. The composition of the cream is a homogeneous mass of white color or white with yellowish color

a slight, mild and pleasant aroma, appropriate to the fat base used. All components of the cream are authorized for pharmaceutical use.

The cream is intended for restoring the epidermal lipid barrier of the facial skin, neck and décolleté in patients with metabolic syndrome.

The cream contains the following components:

Selenomethionine, Se-Met (SEM) - The L-enantiomer of selenium methionine, a natural amino acid containing selenium, is an important source of selenium. Selenomethionine functions as a bioanthoxidate, interacts with vitamins, enzymes, biological membranes in biological systems and the body as a whole. The glutathione peroxidases in the enzyme neutralize oxides and peroxides, protect cell membranes from collapse, perform antihistamines, stimulate collagen, keratin biosynthesis, give skin firmness and elasticity, reduce seborrheic manifestations, activate skin regenerative processes, regenerate skin. Inorganic selenium, selenium disulfide (Selenium disulfide) is used to treat seborrhea of the scalp [37]. According to the US standard, the safe intake of selenium (from the point of view of intoxication) is 50-220 mcg in the daily diet of an adult, according to studies in China were not observed with daily intake of 750 mcg of selenium, but symptoms of intoxication were observed when increasing the daily dose to 5000 mcg / day [38].

Selenomethionine is a hydrophilic substance, the optimal effect of the content of selenium methionine in the cream is 0.0005-0.0015 g. If its content is less than 0.0005 g, the antioxidant effect of the cream is reduced, but if its content is more than 0.0015 g, it is difficult to make the cream, the consistency of the cream has changed, it is not uniform, it makes it difficult to use.

Squalane ((Squalane) - a naturally occurring hydrocarbon of the carotenoid group, a clear colorless and odorless oil. Squalane does not contain double bonds, so it is chemically stable and can be stored for more than 2 years, it does not oxidize and becomes bitter. one of the main components of the skin fat and water lipid mantle. According to dermatocosmetology squalane is a high quality emollient (emollient agent). Squalane is non-comedogenic, unlike triglycerides and fatty acids in the fat layer of the skin [39-10J. Creates a protective film that protects against dehydration, improves respiration of the skin, due to its natural affinity to the skin, squalane is easily absorbed through the epidermis without leaving any grease, and at the same time makes the skin soft and silky. In this synthesis, it has a mild antibacterial effect and helps prevent age spots. Optimal effect of squalane content in the cream 11.25-18.75 g. At a content of less than 11.25 g, the effect of softening and rejuvenating the skin structure was significantly reduced, but at a content of greater than 18.75 g, difficulties were encountered in the preparation of the cream, the stability of the composition was reduced, the cream peeled and application was difficult.

Vitamin E, α-tocopherol (Vitamin E, Alpha-tocopherol) - pale yellow, translucent viscous liquid with a mild odor. It oxidizes in the light and becomes dark. Tocopherol is a hydrophobic substance, contains green parts of young plants, vegetable oils, is a natural antioxidant that participates in free radical inactivation, protects cell membranes from collapse, including in the case of ultraviolet radiation, participates in the synthesis of proteins, regenerative pre-processes [41]. The incorporation of vitamin E into the cream allowed for a much faster restoration of the skin's epidermal lipid barrier in patients with metabolic syndrome. Optimal effect of α-tocopherol (vitamin E) content in the cream 0,50-1,50 g. If its content was less than 0.50 g, the effect was greatly reduced, but if its content was greater than 1.50 g, the consistency of the cream changed, it became significantly thinner and its use was difficult.

Methyl 4-hydroxybenzoate (Methyl paraben), СНз (СбЩ (ОН) СОО) - white or cream crystalline powder, poorly soluble in water. It is soluble in warm water, methanol, propylene glycol. It is characterized by a broad spectrum of antibacterial and antifungal activity, and is naturally synthesized in some plants, such as blueberries. It is used against mold and gram-negative bacteria [42]. It is easily and completely absorbed into the human body through the skin or through the gastrointestinal tract, degrades into simpler substances and is rapidly excreted in the urine without accumulation in the body. It is used as a stabilizer and / or extender, effective in very low concentrations, in pure form and in the form of a 0.25% to 5% alcoholic solution. Optimal effect of the content of methyl 4-hydroxybenzoate in the cream 0.05-0.15 g. If its content is less than 0.05 g, the effect of the stabilizer is significantly reduced, but if its content is greater than 0.15 g, the consistency of the cream is changed, the insolubles are noticeable and the use of the cream is difficult.

Glyceryl Monostearate 60 (Glycery Stearate) - A white powder derived from natural stearic acid and glycerin with a pearly-light effect (reflecting light), is a waxy, solid emulsion, emulsifier and thickener, added during the blending phase of stabilization. Used as a stabilizing and structuring component to prevent separation of the hydrophobic and hydrophilic phases of the composition (composition). separation [43]. If its content is less than 2.52 g, the effect of the thickener is significantly reduced, but if its content is greater than 4.20 g, the consistency of the cream has changed, the cream has become very thick and the use of the cream has been difficult.

Cetyl alcohol (Cetyl alcohol, l-hexadecanol), carbon monoxide, a monohydric fatty alcohol, a white solid, is used in the fat base as an emulsifier and / or opacifier, which improves consistency, increases the stability of the water-oil mixture [44]. Recommended grams for use: 3.78-6.29 g. If its content is less than 3.78 g, the effect of the emulsifier is significantly reduced, the cream is peeled off, but if its content is higher than 6.29 g, the consistency of the cream changes, the cream becomes too liquid and the use of the cream is difficult.

Triglycerides medium-chain - an oily solution of coconut oil, water insoluble, miscible with oils [45]. Improves the uniformity of the cream's application to the skin, dissolves lipophilic compounds. Recommended grams for use: 4.72-7.87 g. If its content is less than 4.72 g, the effect of the stabilizer is significantly reduced, the cream is peeled off, but if its content is more than 7.87 g, the consistency of the cream is changed, the cream becomes too liquid, which makes it difficult to use.

White Vaseline (Vaselinum) - A blend of hard and soft high molecular weight hydrocarbons obtained by mixing white ceresin and paraffin with perfume oil [46]. Vaseline is used as a thickener in skin creams and ointments. When applied externally, petroleum jelly promotes the regeneration of the skin's water-lipid protective mantle, prevents fluid loss in skin cells, prevents peeling and cracks. Vaseline is intended to soften the skin of the face and hands, including in cases caused by external factors (sun, wind, temperature changes). If its content was less than 16.05 g, the effect of the thickener was significantly reduced, but if its content was greater than 26.74 g, the consistency of the cream changed, the cream became too thick, which made it difficult to use the cream.

Macrogol-20-glycerol monostearate (Macrogot), structural formula НО- (СНг-СНг-О) _п -Н, a white powder, forms hydrogen bonds with water molecules, is used in medicine and cosmetics as a bonding ingredient, it is also used in ointment base. as a stabilizing and structuring component which makes the composition uniform [47]. The high hydrophilic degree of macrogol allows the most effective homogenisation of the composition in the amount of 4.40-7.34 g by emulsifying the hydrophobic components of the new cream. If its content is less than 4.40 g, the effect of the thickener is significantly reduced, but if its content is greater than 7.34 g, the consistency of the cream has changed, the cream has become too thick, which makes it difficult to use.

1,2-Propanediol (1,2-propylenglycot), СНзСН (ОН) СН2ОН, organic substance, colorless viscous hydroscopic liquid, odorless, humectant, softening and dispersing agent, good solvent [48]. Most low molecular weight organic compounds containing oxygen and nitrogen are completely mixed with it. If its content is less than 6.29 g, the effect of the thickener is significantly reduced, but if its content is greater than 10.49 g, the consistency of the cream is changed, it becomes too thick and the use of the cream is difficult.

The water (Aqua) base contains as part of the "water in oil" emulsion (where water is the hydrophilic part of the emulsion, oil and squalene is the hydrophobic part). Recommended use: up to 100 g. If its content is less than 33.0 g, the effect of the thickener is significantly reduced, but if its content is greater than 34.6 g, the consistency of the cream has changed, it has become too thick and the use of the cream has been difficult.

The new cream formulation was successfully used to obtain a dosage form of 65.0 g (30.0 g) in tubes. All components of the new cream composition, as separate preparations, are authorized for use in dermatology within the scope of the invention. The composition and manufacturing technology of the new cream meet the standard criteria for product safety assessment as required by the European Commission (Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products, Article 11).

I - П. An example of a cream composition

Contains: selenium-L-methionine 0.0005-0.0015; α-tocopherol acetate 0.50-1.50; squalane 11.25-18.75; methyl 4-hydroxybenzoate 0.05-0.15; glycerol monostearate 60 2.52-4.20; cetyl alcohol 3.78-6.29; medium chain triglycerides 4.72-7.87; white petroleum jelly 16.05-26.74; macrogol-20-glycerol monostearate 4.40-7.34; 1,2-Propanediol 6.29-10.49; purified water to 100.0.

The method of obtaining the cream

The complexity of the new cream formulation is due to the fact that squalane, glycerol, triglycerides, petroleum jelly and α-tocopherol are hydrophobic substances, while selenomethionine, macrogol, propanediol are hydrophilic substances.

Method of obtaining the first cream composition

1. Preparation of the hydrophobic part of the cream.

Melt 2.52-4.20 g of glycerol monostearate 60 and 3.78-6.29 g of cetyl alcohol in a water-bath in a water bath at 65-70 ° C, add and melt 16.05-26.74 g of petroleum jelly, add 11, 25-18,75 g squalane and 4,72-7,87 g medium chain triglycerides, stir until homogeneous. The temperature of the alloy should be 60 ° C.

2. Preparation of the hydrophilic part of the cream.

Dissolve 0.05-0.15 g of methyl 4-hydroxybenzoate in a glass beaker 6.29-10.49 g of 1,2-propanediol at 45-50 ° C, add some of the residual purified water, mix, add 4,40- 7.34 g of macrogol-20-glycerol monostearate are dissolved by heating to 60 ° C.

3. Cream. Add the hydrophilic part to the hydrophobic part in the preparation container, stir in the cream mixer for 15-20 minutes until the mass has cooled to 30-35 ° C.

4. To the weight of the cream add 0,50 to 1,50 g of α-tocopherol acetate and 0,0005 to 0,0015 g of selenium L-methionine dissolved in some of the purified water. Stir the cream in the mixer for 10 minutes until homogenous.

The method of obtaining the second composition is analogous to the first. The resulting cream is packaged in aluminum tubes of 65.0 g (30.0 g each).

The composition of the cream is a homogeneous mass of white or white with a yellowish tinge, with a slight and pleasant aroma, corresponding to the fat base used.

The cream is intended for restoring the epidermal lipid barrier of the facial skin, neck and décolleté in patients with metabolic syndrome. The cream has the biosadenba component and is easily absorbed into the skin by applying a thin, elastic layer to the cream pH 4.0-5.0. The cream has a soothing effect on the skin, it relieves itching and inflammation, it does not cause irritations and side effects after prolonged use.

A prospective clinical study was conducted to evaluate the properties of the cream in the prevention and / or restoration of the epidermal lipid barrier of the skin using the LIPEX (Riga) Dermatology Clinic and Aesthetic Medicine Base. metabolic syndrome aged 39-55 years. As a result, 2 homogeneous patient groups with metabolic syndrome who do not smoke, do not attend a solarium, and have a moderate degree of insolation (moderate sun exposure, spend all season in Central and Northern Europe). The first group (group 1, n = 12) and the second group (group 2, n = 15) included patients diagnosed with metabolic syndrome. The diagnosis of the metabolic syndrome was based on a set of changes, according to the International Classification of Diseases (10th Edition) [1] and analysis by specialists at the US National Institute of Health: Metabolic syndrome was defined by three or more symptoms:

• Abdominal type of obesity - waist circumference greater than 89 cm in women and greater than 102 cm in men • fasting glucose level greater than 6.1 mmol / l • triglyceride level greater than 1.69 mmol ·! • low Decreased density of lipoproteins: in women less than

1.29 mmol / l; men - less than 1.04 mmc ^ l / 1, • arterial blood pressure level 135/85 mmHg.

The study protocol, agreement and membership protocol, the membership questionnaire are in accordance with the World Medical Association's (PMA) Helsinki Declaration of Ethical and Humanistic Principles in Medicine, and approved by the Riga Stradins University Ethics Commission. There is no conflict of interest.

In Group 1 patients (n = 12), after previous examination, the cream was administered over a long period (2 months, during active UV insolation, in May and June). The cream was applied in a thin layer, twice a day (morning and evening), on clean face, neck and décolleté areas. Group 2 patients did not use the cream. In both groups, clinical trials were repeated at 14, 30 and 60 days after the start of the cream application.

Clinical trials included anthropometric data (body mass index, waist circumference, arterial blood pressure), blood tests (glucose, lipoproteins). Siascopy and dermatoscopy (Sole MoleVievv SIAscope V Handset, Astron, UK and HEINE alpha + Heine Optotechnic, Germany) were performed to evaluate the epidermal lipid barrier of the skin. Dermatoscopy assessed skin relief and morphology (turgor, microrelief, and presence of papillomas). Pigmentation and flaking were evaluated using siascopy. The pH-metry was measured with the aid of a pH-meter. Transepidermal water loss was measured using a Tewameter® TM 300 (Courage + Khazaka electronic GmbH, Germany) (Toulameter) sensor. Study results obtained with these sensors were calculated and saved using software in database SPSS20.0 (Microsoft :, USA). The results were recorded in numerical values. Normal values for cornealometry ranged from 40 and higher, to those below 12, and to pH-metric values between 5.5 and 5.8. Each trait was rated on a scale of 0 to 3: 0 - no trait, 2 - moderate, 3 - strong.

Structural change data were evaluated and skin immunity was assessed: histological studies were performed using light microscopy. Light microscopy magnification - 400-fold by immunohistochemistry using CDla, CD31, CD34, CD3, CD8.

Table 2 - Results of clinical trials in both patient groups with metabolic syndrome.

Table 2

Group 1, New Cream, n = 12 Group 2, no cream applied, n = 15 Leather turgor (0-1-2-3 on scale) medium, high medium low Moisturizing Transepidermal water loss and comometry 27.2 ± 1.1 19.1 ± 1.2 Peeling (0-1-2-3 on the scale) Average index 1.8 Large cell content 34.4% Average index 2.6 Quantity of large dogs 65.7 + 5% Lentigo, pigmentation Average index Average index unevenness (on a scale of 0-1-2-3) 1.2 2.8 PH ............. Within the range 5.5-5.8 Within the limits of 5.4 to 5.6 Skin relief (0-1-2-3 on the scale) Average index 1.6 Average index 2.8

In the study, the majority of patients in both groups had complaints of dry skin and increased exfoliation.

In clinical studies, patients in group 1 (12) who had been using the cream for 2 months had the following parameters: 1) skin moisture was 27, 2 ± 1, ie higher compared to group 2 (15) - 19, 1 ± 1.2; 2) Exfoliation - 1.8 was in Group 1 patients and 2.6 was in Group 2 patients, i.e. exfoliation was more pronounced in Group 2 patients; 3) Pigmentation - 1.2 was in Group 1 patients and 2.8 in Group 2 patients, i.e., pigmentation was more pronounced in Group 2 patients; 4) Skin relief - 1.6 was in group 1 patients and 2.8 was in group 2 patients, i.e., the presence of papillomas and skin elastosis were more pronounced in group 2 patients.

Thus, in Group 1 patients who received the new. cream within 2 months, restoration of skin barrier function, skin relief and elasticity.

Skin immunity cells (Langerhans cells) showed reduced activity in Group 2 patients, according to data from skin immunity studies. In addition, lymphocytic infiltration and accumulation of Birbeck's granules (indicative of an inflammatory process) were observed in the skin of patients in group 2. In the skin of patients in Group 1, the amount of immunocompetent Langerhans cells increased in the background of the new cream, with a doubling of Birbeck's granules, indicating an improvement in local skin immunity.

Studies have shown that the new cream composition has cosmetic and therapeutic properties, restores the skin's epidermal lipid barrier and skin barrier function in patients with metabolic syndrome: improves skin turgor and moisture, restores elasticity and smooth skin relief, reduces the appearance of pigmentation, .

The complexity of the invention is due to the lack of knowledge of the components of the new composition and their relationship, which would allow the new composition to exert an effective restorative effect on the epidermal lipid barrier of the skin. The development of the cream was further complicated by the fact that the components of the new composition were both hydrophilic (selenomethionine) and hydrophobic (vitamin E, squalane) substances. The conditions under which the hydrophilic and hydrophobic components of the new formulation could be compatible in a single cream with a high degree of grease were not known. . Experimentally obtained components, their mutual ratio and technological conditions for obtaining the new cream composition allowed to produce a stable homogeneous composition of the new cream, which retains its effectiveness and stable consistency at room temperature for 6-8 months.

The composition of the new cream is a mixture of water and fat, greasy and other substances. The high percentage of field and greasy substances is important to achieve the effect of restoring the skin's epidermal lipid barrier and water-lipid mantle. There is a technological difficulty in blending such a number of fats without the risk of delamination of the finished product. For these types of creams, it is important to use special emulsifiers, the inclusion of which in the claimed ratio allows a uniform creamy consistency of the new cream composition, which maintains stability during storage and convenient extrusion of the finished dosage form from the package. The difference in composition of the claimed new cream is due to the fact that several substances are used as emulsifiers, each of which has structuring and emulsifying properties. Concomitantly used emulsifiers which are introduced into the cream in a strictly sequential order, according to the technology of the claimed invention, provide an effective and stable preservation of the complex composition of the new cream. A certain ratio of hydrophilic components (water, selenomethionine, glycerol) and a certain ratio of solvents (cetyl alcohol, glycerol) allows the activity of hydrophilic (selenomethionine) and hydrophobic (tocopherol, squalane, triglycerides) substances contained in the cream composition to be maintained.

The composition of the new cream was not found in scientific and patent sources. Experimental and clinical studies carried out indicate compliance with the criterion of "inventive step"

INDUSTRIAL USE

Developed in 2 industrial cream shapes - 65.0 g (30.0 g each) in light-proof aluminum tubes. The stability and technological properties of both formulations of the new cream are maintained for 6 months at room temperature.

Sources of information

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Claims (2)

1. Cream for restoring the epidermal lipid barrier of the facial skin, neck and décolleté in patients with metabolic syndrome characterized by the presence of selenium L-methionine, α-tocopherol acetate, squalane, methyl W-hydroxybenzoate, glycerol monostearate 60, cetyl alcohol, medium chain triglycerides, white petroleum jelly, macrogol-20-glycerol monostearate, 1,2-propanediol and purified water. Cream for restoring the epidermal lipid barrier of facial skin, neck and décolleté in patients with metabolic syndrome according to claim 1, characterized in that it contains selenium L-methionine, α-tocopherol acetate, squalane, methyl 4-hydroxybenzoate, glycerol monostearate 60, cetyl alcohol , medium chain triglycerides, white petroleum jelly, macrogol-20-glycerol monostearate, 1,2-propanediol and purified water in the following weight ratios g (%): selenium-L-methionine 0.0005-0.0015; a — tocopherol acetate 0.50-1.50; squalane 11.25-18.75; methyl 4-hydroxybenzoate 0.05 0.15; glycerol monostearate 60 2.52-4.20; cctils alcohol 3.78-6.29; medium chain triglycerides 4.72-7.87; white petroleum jelly 16.05-26.74; macrogol-20-glycerol monostearate 4.40-7.34; 1,2-Propanediol 6.29-10.49; purified water to 100.0.